The influence of opioid peptides on alcohol sensitivity has been studied for a number of years, and the endogenous opioid system is hypothesized to be an important substrate for alcohol actions. The experiments proposed in this application will utilize transgenic mice that differ in their ability to synthesize B-endorphin in order to study the way that B-endorphin affects the response to alcohol. We have shown that these mice differ with respect to self-administration of alcohol. Other preliminary data indicate that mice lacking B-endorphin have an enhanced alcohol-mediated reduction in anxiety - in spite of the fact that under basal conditions anxiety increases as B-endorphin levels decrease. In addition, B-endorphin deficient mice show increased sensitivity to EtOH-induced ataxia and analgesia. These data support the hypothesis, deriving from both clinical and basic research, that B-endorphin affects sensitivity to alcohol. The overarching aim of these studies is to more fully characterize alcohol's differential effect on behavior in mice possessing varying amounts of B-endorphin. Moreover, we are hopeful that a better understanding of the relationship between alcohol and B-endorphin levels will lead to studies in which the mechanism of interaction can be elucidated. Because this peptide appears to differ between humans with varying genetic risk for alcoholism, a greater understanding of its relationship to alcohol sensitivity will contribute to our knowledge of the mechanisms underlying excessive alcohol use.